BRYCE L. CRAWFORD, JR., one of the nation's prominent chemists, passed away due to congestive heart failure on 16 September 2011 at Presbyterian Homes in Arden Hills, St. Paul. He was 96. In 1982, the American Chemical Society chose to honor Dr. Crawford with the Priestley Medal, its most prestigious award, for his outstanding lifetime contributions to the science.Bryce was born in New Orleans on 27 November 1914 to Low Crawford and Clara Hall Crawford. In 1940, he married Ruth Raney in Chicago. They had three children, L. Crawford III (Davenport, Iowa), Craig Crawford (Richmond, Virginia), and Sherry Crawford (Vinton, Iowa), and eight grandchildren.Bryce grew up mostly in the San Francisco Bay Area and also in El Paso. His youth was remarkable as well. He skipped several grades, quickly advancing his education. He was the youngest student at 15 to graduate from El Paso High School. In 1931, representing the state of Texas, he won first place and obtained $500 in the National Edison chemistry essay contest. He was flown to Menlo Park, New Jersey, for his award, and there he met Henry Ford and Thomas Edison. As a teenager, spent summers working as a ranch hand on Jimmy Mayhill's ranch in the hills of Alamogordo, New Mexico.He enrolled at Stanford University and received his A.B. degree in 1934, an A.M. degree in 1935, and a Ph.D. degree in chemistry in 1937, with the supervision of Professor Paul C. Cross. He then spent 2 years at Harvard University as a National Research Fellow, working in the laboratories of Professor E. Bright Wilson, Jr. This seems to have strongly influenced the direction of his future progress in science. He also spent a year at Yale University as a chemistry instructor. In 1940, he joined the chemistry department of the University of Minnesota, and in the same year, his bride, Ruth, arrived by train in St. Paul in the middle of the Armistice Day blizzard.At the University of Minnesota, started as an assistant professor of physical chemistry, but rose swiftly and became a full professor in 1946, chairing the chemistry department from 1955-60 and serving as dean of the graduate school from 1960-72. During this period, he organized, with Professor John Overend, the Minnesota Summer Course in infrared spectroscopy, with co-sponsorship of Perkin-Elmer. This short course greatly helped to give industrial spectroscopists an opportunity to update their understanding of molecular vibrations and the interpretation of infrared spectra. At that time, the infrared instruments were placed in the basement area of the chemistry department; had a nicely lettered sign over the narrow entrance lane designating the area as Bryce Canyon.In 1950-51, spent time at the California Institute of Technology as a Guggenheim Fellow and at Oxford University as a Fulbright Fellow in the field of molecular spectroscopy. He was selected to be a Fulbright Professor in Japan in 1966 and collaborated with Professor Takehiko Shimanouchi, who practically contributed to calculations of molecular vibrations using force constants. Bryce, on the other hand, developed the first principle method of calculating force constants from molecular orbitals.During World War II, worked on rocket propellants, carrying out research in his own laboratories at Minnesota and also at the Allegany Ballistics Laboratory in Cumberland, Maryland. His work was a significant contribution to World War II rocketry and the development of solid propellants for the much larger rockets that evolved after the war. But his first love was always chemistry. His focus and interest centered on molecular spectroscopy and molecular structure.Among Bryce's many accomplishments and involvements, those that meant the most to him included his years as home secretary for the National Academy of Sciences (NAS) and his chairmanship of the NAS report review committee. The committee's work was to see that the scientific findings and reports it released were thorough, objective, and complete. …

INTRODUCTIONThis essay considers environmental and life-style factors in natural selection during the three hundred thousand generations that separate us from a great ape ancestor. Humans have the evolved greatest life expectancy (LE) among the primates (fig. 1). The LE at birth of pre-industrial humans, ca. 30-40 years, is twice that of the four extant great ape species (Finch 2007, 2010a; Finch and Austad 2011). The longer human LE is associated with slower postnatal maturation and with lower mortality as adults than the great apes. While these differences are clearly seated in genetics, recent environmental improvements have further increased LE. Since 1800, during industrialization and economic development, the LE doubled again, reaching 70-85 years in favored populations (Christensen et al. 2009). Not only was survival at early ages enhanced, but the LE at age 70 has also more than doubled (Finch and Crimmins 2005). The recent rapid increases in lifespan within ten generations are consistent with environmental factors, rather than genetic selection. The limited heritability of human lifespans, about 25% in identical twins (Herskind et al. 1996; Finch and Tanzi 1997), also shows the importance of environmental and epigenetic factors in aging processes (Finch and Kirkwood 2000; Kirkwood and Finch 2002; Martin 2011). Infection and inflammation have had recognized roles during the recent increases of LE, which I propose were also important in our evolutionary past. Last, I also consider how global environmental deterioration and emerging climate changes could increase global inflammatory exposure and potentially reverse recent gains in LE.MORTALITY CURVE ANALYSISThe huge recent increases in LE are concurrent with the improvements in hygiene, nutrition, and medicine during the nineteenth and twentieth centuries that reduced mortality from infections at all ages. A hypothesis developed with Eileen Crimmins proposes that these reductions in mortality were enabled by a reduced load of chronic inflammation and infection. The load of infection and inflammation is represented by mortality at early ages, which is dominated by infectious causes (Finch and Crimmins 2004, 2005; Crimmins and Finch 2006a; Finch 2007). Inflammation is closely linked to most chronic diseases of aging, including atherosclerosis and cancer (Finch 2007, 2010a,c; Franceschi 2007; Van Den Biggelaar et al. 2004). Consider two textbook examples: The twentieth-century scourge of tobacco smoking is well understood as causing chronic inflammation with oxidative stress that accelerates vascular aging (carotid thickening) and causes DNA damage and increased cancer. The common gut bacterium Helicobacter pylori, once pandemic and now increasingly restricted, increases cancer risk in association with chronic inflammation and DNA damage.The historical shifts in mortality are graphed as mortality rates by historical cohort, which have a J-shaped curve (fig. 2A). Data may be plotted by period, i.e., cross-sectionally, representing all ages present for a given year. Alternatively, tracking a birth cohort across its lifespan reveals additional features of lingering environmental effects. When mortality rates are graphed by cohort, the curves show more distinct trajectories than if plotted by period, with progressive displacement downward across the lifespan during the last two hundred years. The most complete demographic history is from the national data of Sweden since 1750 (Finch and Crimmins 2004; Crimmins and Finch 2006a,b).Four phases can be resolved in human mortality curves: Mortality Phase 1, decreasing mortality from birth to puberty (0-9 years); Phase 2, basal mortality, which is the lowest during the lifespan (10-40 y); Phase 3, exponentially accelerating mortality (40-80 y); Phase 4, asymptoting mortality (>80 y), which approaches a maximum of 0.5/y after 100. The acceleration of mortality in adults, during the long ascending Phase 3, is described by the Gompertz exponential model:m(x) - Aexp(Gx) Eq. …

HUMAN SKIN is remarkable and, in several ways, unique. It is mostly naked, it is sweaty, it is tough yet sensitive, and it comes in a range of colors. The plentiful sweat glands in human skin secrete watery fluid that evaporates and helps to cool us when we are hot, and the outer surface of our skin is rich in specialized keratin proteins that help the skin to resist physical and chemical insults while remaining exquisitely sensitive to touch. The pigmentation of human skin is of greatest interest here. The array of colors found in human skin is greater than that seen in any other mammalian species.People with darkly and lightly colored skin differ in their skin reflectance, the amount of visible light that is actually reflected from the surface of their skin. This difference can be visually striking and has spurred questions for several centuries as to how variation in skin color came about. One of the problems in studying the evolution of human skin is that it is absent from the fossil record. It generally decays soon after death, leaving no traces of its composition or color behind. Evolutionary biologists seeking to understand the evolution of skin must thus resort to other means, including comparative anatomy, physiology, and molecular genetics.The range of skin colors found in humans contrasts with the condition seen in our closest primate relatives, which have light skin covered by dark hair. This condition is typified by our closest living relatives, chimpanzees (fig. 1), which are born with uniformly pale skin. Glabrous skin on the face and hands darkens after exposure to the sun so that, after a few years of life, the infant's face becomes mottled and eventually becomes uniformly dark like that of its mother. The skin of the rest of its body, protected from the sun by hair, remains pale. The ability to produce melanin pigment in specialized cells called melanocytes in the skin in response to ultraviolet radiation (UVR) is a characteristic shared by humans and their closest relatives, the apes and Old World monkeys (Jablonski and Chaplin 2000). We can infer that this condition was present in the common ancestor of chimpanzees and humans six million years ago (Ma).Reconstruction of the nature and likely appearance of the skin of the fossil relatives of humans - generically referred to as hominins - is possible using a wide range of methods and techniques available to comparative biologists, including comparative and functional genomics. One of the best-known hominin species is Australopithecus afarensis, a species that lived in eastern and northeastern Africa between 3.6 and 2.9 Ma and became widely known through the well-preserved fossil partial skeleton nicknamed Lucy (AL 288-1) from the site of Hadar in Ethiopia. Reconstruction of the posture and locomotion of the species from its limb proportions and joint anatomy indicates that, although bipedal, A. afarensis was more of a deliberate walker and climber than a long-distance strider and runner (Jungers 1988). Its normal range of activities was probably closer to that of modern chimpanzees than to that of modern humans, and this generally would not have resulted in individuals' building up excess heat as the result of prolonged activity. We can infer that members of this species possessed skin similar in anatomy and appearance to that of modern chimpanzees (fig. 2). The timing of the loss of body hair in hominins can be inferred by similar means: examination of the skeleton and reconstruction of the mode and intensity of locomotion. The uncommonly well-preserved skeleton of an early member of the genus Homo from the site of West Turkana (WT-1 5000), aged about 1.5 Ma, indicates that functional modernity in gait and activity pattern had been achieved by this time, specifically, that they were engaging in extended bouts of vigorous exercise, which would have resulted in the build-up of excess body heat (Bramble and Lieberman 2004). These hominins lived in hot equatorial environments, and had to cope with high external heat loads in addition to those generated by elevated metabolism. …

SEVERE OBESITY is associated with a large number of comorbid diseases. These start at the head (stroke, diabetic retinopathy, pseudotumor cerebri, tinnitus) and go to the toes (diabetic neuropathy, foot ulcers, venous stasis disease) and affect almost every organ in between: lungs, heart, liver, spleen, gall bladder, esophagus, intestines, colon, kidneys, bladder, ovaries, prostate, breast, kidneys, bladder, legs, etc. Many of these comorbidities can be divided into two major groups: the metabolic syndrome (also known as Syndrome X) and comorbidities secondary to an increased intra-abdominal pressure (1). Metabolic syndrome comorbidities include type 2 diabetes mellitus (T2DM), hypercholesterolemia, hypertriglyceridemia, non-alcoholic liver disease (NALD) or steatohepatitis (NASH), polycystic ovary syndrome, hypertension, and gallstones. The comorbidities associated with an increased intra-abdominal pressure include pseudotumor cerebri, obesity hypoventilation, venous stasis disease (venous thrombosis, venous stasis ulcers, pulmonary embolism), gastroesophageal reflux disease (GERD), urinary stress incontinence, abdominal hernias (inguinal, umbilical, incisional), hypertension, and the nephrotic syndrome. Other problems such as sleep apnea, diverticulitis, necrotizing pancreatitis, and musculoskeletal disorders (low back, hip, and knee pain), as well as depression and quality of life (QoL) issues are unrelated to either the metabolic syndrome or increased intra-abdominal pressure. Severe obesity also increases the risk of developing cancer (esophagus, liver, pancreas, kidney, colon, breast, uterus, ovary, prostate, leukemias, lymphomas), some of which are associated with the metabolic syndrome (e.g., breast, uterus, prostate) and some secondary to an increased intra-abdominal pressure (e.g., esophagus). Severe obesity is also associated with severe discrimination, problems with employability, and absenteeism, as well as presenteeism (limited quality and quantity of work when employed).Unfortunately, dietary management with or without pharmaceutical therapy has not been effective over the long term (three to five years) for severely obese individuals. Weight loss peaks at approximately 10% of weight, but recidivism is almost invariable. Bariatric surgery is associated with the loss of approximately one-third of pre-operative weight or two-thirds of excess weight, and this weight loss is reasonably stable over ten years, with a relatively small degree of recidivism (2-4). In 1991 the National Institutes of Health Consensus Conference supported bariatric surgery in patients with a body mass index (BMI) of 35 kg/m2 and obesity-related comorbidities or a BMI of 40 kg/m2 regardless of comorbidity status (5).The current operations for severe obesity include Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric band (LAGB), biliopancreatic diversion (BPD) with or without a sleeve gastrectomy (SG), and an SG by itself (figs. 1-4) (6-9).Surgically induced weight loss is associated with a significant improvement in or remission of all obesity-related comorbidities. In a study by Christou et al. there were significant improvements after RYGB in patients from Quebec, Canada, in musculoskeletal disorders, infectious complications, endocrinological problems, cardiovascular complications (myocardial infarction, peripheral vascular disease), respiratory problems (sleep apnea, obesity hypoventilation), mental problems, genitourinary problems, and, for the first time, a significant decrease in cancer care (10). In a meta-analysis with 22,094 patients, Buchwald et al. found a significant improvement in T2DM (86%), hyperlipidemia (70%), hypertension (62%), and sleep apnea (86%) following bariatric surgery (11). In that study, there was significantly more weight loss with the RYGB and BPD than with the LAGB, and these were associated with a better improvement in T2DM than the LAGB. The LAGB had the lowest mortality risk (0. …

TRANSPLANTATION OF A LIMB or face has been a logical extension of organ transplantation. The feasibility of transplanting organ allografts2 was demonstrated for the first time with kidneys in 1959. During the preceding 15 years, it had been established that rejection of skin allografts in experimental animals (1) and humans (2) is an immunologic response and that analogous events cause destruction of canine (3,4) and human kidney allografts. The only exception was with identical twins, between whom tissues and organs (isografts) can be freely exchanged (5,6).Before 1959, most of the human kidney allografts were transplanted to non-immunosuppressed recipients.3 The kidneys were obtained from recently deceased persons (e.g., in France after guillotine execution) or in the United States from surgical patients from whom a kidney was removed for a variety of non-transplant objectives (7-12), and from a mother in France who was the first recorded living organ donor (for her son) (13).No matter what the source of the renal allografts, the pace of the rejection was much the same and was complete in a few days or weeks. Efforts up to 1959 to prevent the rejection of renal allografts by weakening the recipient immune response with irradiation or drug immunosuppression had failed to produce kidney allograft survival in humans or in any animal model for as long as 30 days. Consequently, the successful kidney alloengraftments accomplished in humans between 1959 and 1963 (table 1) were surprising to almost all immunologists, physicians, and surgeons.In retrospect, however, there had been clues suggesting the theoretical possibility of organ alloengraftment, beginning with observations in cattle. In these bovine fraternal twins, the placentas are fused during uterine gestation, allowing fetal cross-circulation (fig. 1, inset I).4 In 1945, it had been reported by Ray Owen (APS 1984) that each member of a freemartin pair contained the other's blood cells after birth and throughout life (persistent blood chimerism) (14).The blood chimerism subsequently was incorporated by the Australian Macfarlane Burnet (APS I960) in the clonal selection theory of immunity that became the cornerstone of modern immunology (15). As part of his hypothesis, Burnet predicted that the cattle twins would be able by virtue of their chimerism to freely exchange all tissues. In 1952, Peter Medawar (APS 1961) and his English team validated this prediction with skin graft experiments in both same-sex and cross-sex cattle twin pairs (16), and then proceeded in 1953 to demonstrate that similar non-responsiveness (acquired immunologic tolerance) could be deliberately produced in mice.In the mouse experiments, Medawar and his associates, Rupert Billingham and Leslie Brent, transplanted allogeneic spleen cells from adult donors into immunologically immature animals (17,18) (fig. 2, outer rim). This was the forerunner model of bone marrow cell transplantation for humans afflicted with immune deficiency diseases (fig.l, inset 2a). In a second model, Main and Prehn (19) in Bethesda reduced the immune responsiveness of adult recipient mice by total body irradiation prior to the transplantation of bone marrow cells (fig. 2, center). This model ultimately evolved into clinical bone marrow transplantation for a wide range of hematologic and other indications (fig. 1, inset 2b). Under both circumstances depicted in figure 2, the mouse recipients engrafted with donor leukocytes could accept other tissues from the same donor. Thus, the strong association of acquired donor-specific tolerance with donor leukocyte chimerism was formally established.A three-step strategy derived from the mouse experiments that could permit organ engraftment in patients was promptly envisioned by surgeons (20,21). It consisted of weakening the recipient's immune system with total body irradiation as had been done by Main and Prehn, infusion of donor lymphopoietic (e. …

FACE TRANSPLANT has emerged from ethical debate to surgical reality. Nine face transplants have been realized in the world in the last four years. However, collecting data is difficult, and only long-term follow-up will show the real indications and risks. The place of face transplant in the future of plastic surgery is thus unclear. However, all plastic surgeons confronted with improbable cases have thought of face transplant as a possible solution.Looking back at our first case with two years of follow-up, it is clear that in selected cases the results can be excellent with minimal immunosuppressive treatment. This patient, who had neurofibromatosis, was the modern elephant man. He had multiple operations by very skilled plastic surgeons, with no results. After his transplant, he was able to find a job and go back to a normal life.But how did we get to this point? We should first go back in history to see where reconstructive surgery started and what are the challenges that we face today.Before the Renaissance, surgeons were on the battlefield showing their skill in quickly removing bullets and cutting off legs, competing to be the most efficient. Then came anatomy, brought to us by Andrea Vesalius (1514-1564) in its founding book De Humants Fabrica. With this knowledge of the constitution of the body, Ambroise Pare (1510-1590) in France first showed that ligature of blood vessels could be more efficient than the burning of a wound as a means of avoiding bleeding, and showed how to know which internal organ could be damaged just by looking at bullet wounds in a scientific manner from which today's experts could learn. But the mysteries remained. As he said, I do the dressing, but God does the healing. He showed us the way to repair, not to reconstruct. Gaspare Tagliacozzi (1545-1599) is considered the first reconstructive surgeon of Western countries. He is well known for his nose reconstruction by harvesting a flap on the arm of a patient. Once raised, the flap was brought to the face and sutured while still attached to the arm. The patient would stay in this uncomfortable position for three weeks. The distal part of the flap was then divided, and the flap, still attached to the nose, was shaped to form a new nose.The English brought another technique to Europe in the eighteenth century, during the conquest of India. An amputated nose could be reconstructed from a forehead flap that was rotated and shaped to form a nose. This strange procedure, published in the Gentleman's Magazine in 1794, came into competition with Tagliacozzi 's Italian graft, and during all the nineteenth century those two techniques were used.The First World War brought to surgery numerous patients, who founded in France the gueules cassees (broken faces) association. Most of them were treated in the Val-de-Grâce Hospital in Paris, where the casts of those broken faces can still be seen. Hippolyte Morestin (18691919) was the facial surgeon in the Val-de-Grâce. He developed numerous techniques, some of which are still in use today. He died of the Spanish flu and was followed by other surgeons like Harold Gillies (1882-1960), who is considered by the English-speaking countries to be the father of modern plastic surgery. The Second World War brought numerous facial injuries. Most of these injuries involved burns of the face and hands. The pilots of the RAF made up a large part of the patients. Sir Peter Medawar (1915-1987), who received the Nobel Prize in 1960, studied the immunology of skin grafting. After World War II, other techniques were developed to improve facial reconstruction. Paul Tessier (1917-2008) in France showed the world how to cut the facial bones to advance the face or move the orbits.In the late seventies, following the work of Harry Buncke (19222008) in the U.S., the field of reconstructive microsurgery was developed. This innovation used special instruments and magnification devices and allowed the repair of vessels less than one millimeter in diameter. …

SNAKING OUT of the MRI tube where I had lain for the past half hour, I glimpsed Dr. Hanna Damasio studying the lab's dis play screen. Off the gurney, I went to her side and stared at the image of my brain on the screen. Is that—me? Well, yes, in a certain sense. And yet not simply, or merely, me. Certainly not familiarly me. Here is what I thought: Somehow, starting in infancy, my brain built a story about itself—its body, its history, its 'now,' and its world. From the inside, I know that story—though I think of it as reality, not just a story. Indeed, it is my inner reality. So how does this happen? What is it for me to be a construction of my brain? In one form or another, these questions have had a long and convo luted history, born in the unflinching curiosity of the ancient Greeks, and finding voice in diverse cultures. Until recently, the only explana tory resources for addressing puzzling behavior depended on mytholo gizing in the case of others, and myth-filtered introspection in the case of oneself. Not surprisingly, early explanations invoked possession by devils or, if you were luckier, divine forces, to account for epileptic sei zures or schizophrenic hallucinations. In the absence of understanding, the punishment theory of mental dysfunction commanded widespread belief, yet it was wholly untestable—and essentially untested. Melancholia (what we now call chronic depression) and phobias were often surmised to be essentially character flaws—flaws that might be overcome with sufficient gumption. The existence of witches, hexes, curses, and spells had a far longer history as brute fact than does our appreciation of such potent neurochemicals as serotonin. Obsessive hand washing, a mere fifteen years ago, was widely assumed to be a manifes tation of repressed sexuality. Nevertheless, even as early as 400 BC, the great Greek physician, Hippocrates, was convinced that events such as

MOVEMENT IS PROCESSED at multiple levels of the CNS. One key region for motor control is the primary motor cortex (Ml). This area, which sends direct motor commands to muscles via the cortico-spinal pathway, contains a detailed somatotopic map of our body, known as the motor homunculus. The concept of homunculus, first described in humans by Penfield (1950), refers to a collection of anatomically and functionally segregated representations of individual body segments along the central sulcus. Although this classical textbook picture of the motor body schema is widely accepted, there is an unresolved controversy regarding how strict this somatotopy is and, related to this issue, whether body parts are represented in Ml as individual muscles or as integrated movements. According to the hypothesis, pools of adjacent neurons represent discrete muscles and are organized in a rigid somatotopic manner, while the movement hypothesis postulates that the motor map represents motor synergies between several muscle groups. At the root of this controversy are observations made both in human Ml and in its non-human primate homologue, that the same muscle or muscle group can be represented in multiple and sometimes non-adjacent subregions of Ml.Although the functional organization of Ml clearly includes separate representations of face, arm, and leg, recent studies have shown considerable overlap and intermingling of representations of smaller body parts. In monkeys, a single neuron may be active during movements of different digits, and the cortical territories containing neurons active during movements of different digits show considerable overlap (Schieber and Hibbard 1993). Functional Magnetic Resonance Imaging (fMRI) studies in normal subjects confirm the existence of spatial overlap in the motor cortex for movements that involve adjacent corporal segments such as the fingers, wrist, and elbow (Sanes et al. 1995; Lotze et al. 2000). Thus, there seems to be a mosaic-like representation of muscular groups (Sanes et al. 1990; Donoghue et al. 1990), suggesting that body parts are controlled by a distributed network in Ml, probably because it is an efficient way of encoding multi-segment motor synergies (Sanes and Schieber 2001). Recent work in monkeys (Graziano et al. 2006) goes further by showing that long train stimulation can evoke complex, ethologically relevant movements not only in the premotor regions, but also in the primary motor cortex.Data from monkeys and human patients suffering from upper-limb amputation show the great interaction that exists between major representations within the motor area. In non-human primates with accidental amputation of the digits, intracortical microstimulation of Ml in the region normally representing the missing segment yields muscular contractions in the stump and in neighboring areas (Schieber and Deuel 1997; Wu and Kaas 1999). Human studies have likewise shown that the representation of the unaffected muscles expands in such a way that the representation of the arm invades portions of Ml previously dedicated to the amputated hand (Cohen et al. 1991), suggesting that former hand neurons are reassigned to the control of proximal upper limb movements.Interestingly, cortical activation in the primary motor and sensory cortex evidenced in patients able to perform movements of their phantom limbs indicates that the areas devoted to the missing limb are functional, sometimes many decades after amputation (Kew et al. 1994; Lotze et al. 2001; Roux et al. 2003). Phantom movements can be evoked by magnetically stimulating stump muscles representations in M1 (Hess et al. 1986; Cohen et al. 1991; Pascual-Leone et al. 1996; Mercier et al. 2006), and electromyographic recording patterns collected from remaining upper arm muscles while the patient attempts to move the stump clearly depart from movements aimed at the phantom limb (Reilly et al. 2006), indicating that hand motor repertoires still exist in the motor cortex after amputation. …

DURING THE PAST DECADE, composite tissue allografts (CTAs) have pioneered a new era in transplantation history. Together with knee joint, larynx, abdominal wall, arm, and even penis allografts, allografts of hands and face belong to CTAs. Most of these grafts are visible and are not vital. They are life-enhancing rather than life-sustaining, but, in words of first transplant patients, they are truly life-giving, and not just life-saving.The introduction of CTAs posed three great challenges. The first was immunological. CTAs are a combination of tissues of diverse embryological origin, histological structure, and function. Each tissue is different in terms of immunogenicity and rejection pattern, and one rejection might cause rejection of other tissues. The skin, which constitutes natural barrier with outside world, is most immunogenic tissue of body and most readily rejected, and fear of skin rejection is most likely explanation for late introduction of CTAs compared with organ transplantation. Bone marrow is also aggressively rejected. This is a well-known phenomenon in clinical bone marrow transplantation. The second challenge was technical. Several surgeons with complementary competencies and experiences had to master both conventional and microsurgical techniques. The first hand and face transplants were performed by international teams of surgeons, whom I consider to be among best in their fields. The third challenge was psychological. In my mind, it was a major challenge. In 1966, when dream of hand transplantation was dawning thanks to hypothesis of hematopoietic stem cell migration, technique in current use was hand replantation on same person. The question that badgered me was this: Is it possible to see and use hands of a dead person, day in, day out? Discussions with Jean Cournut, a leading psychoanalyst at head of Freudian school in France, led us to conclusion that hand appropriation was possible. However, we overestimated impact of amputation on body image and underestimated its impact on function. On advice of Jean Cournut, I worked with his colleague, Gabriel Burloux in Lyon, who became a key member of our team.HAND AND FACE ALLOGRAFTSThe hand with its opposable thumb was a key factor in evolution of humankind and in its domination over other species. The hand plays an essential role in communication with our fellow men, adding colorfulness and expression to language. The hand can wave, give, and caress; it can pick up, grasp, and hold; it can write and sign its name; it can squeeze, punch, fight, strangle, and pull trigger. In so doing, hand forges our identity. Moreover, we cannot ignore practical and symbolical significance of fingerprint.Our faces characterize us in our own eyes and in that of humankind. Our faces enable us to speak, eat, and drink. They can laugh, smile, and kiss; they can express tenderness and love; they can also cry and be sad. They can show scorn and anger, bite, and spit. Our faces reveal our inner self, our individuality, and above all our identity.Our hands and face raise question of what it means to be human. They constitute boundaries between symbols and reality, and are essential to our body image. In 1935, Paul Schilder defined body image as the picture of body which we form in our mind. Although this definition does not add much to term itself, it does have advantage of linking hand and face to brain. The hands and face collude with brain. They enable us not only to project ourselves onto others, but also to perceive ourselves through our interactions with others. When our body undergoes injury, so does our body image. These injuries are narcissistic wounds, and boundaries between somatic and narcissistic wounds overlap. In an article about challenges of face transplantation published in a 2004 issue of American Journal of Law & Medicine, Rhonda Gay Hartman asked a fundamental question: What is value of a human face? …